Abstract
Otitis media (OM) is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by mucous cell hyperplasia that is thought to produce mucins from the middle ear mucosa. We are interested in the role of Notch signalling pathway in this inflammatory process. Using an acute otitis media (AOM) mouse model through injection of Streptococcus Pneumoniae into the middle ear, histopathologic examination and quantitative RT-PCR, acute inflammation with the thickness of mucosa, Goblet cell hyperplasia, and cilia loss were determined and gene expression related to the Notch signaling pathway were evaluated. Upregulation of the mucous cell markers, Argr2 and Muc5AC, and downregulation of the cilia cell marker, Foxj1 and Dnai2, were observed in AOM. In addition, genes encoding Notch receptors and ligands (Notch1, Notch2, Notch3, Notch4 and Dll1) and the Notch target genes (Hes1, Hes5, Hey1, NRARP) in AOM decreased significantly. The expression of the Notch1 and Jagged1 also showed down-regulation throughout the mouse middle ear epithelium. Taken together, this study suggests that downregulation of the Notch signaling pathway is involved in the mucosa hyperplasia during AOM.
Highlights
Goblet cells are mucus secretory cells that are scattered among the columnar cells near the Eustachian tube orifice in the middle ear epithelium
An accumulation of fluid in the middle ear and mucous cell metaplasia-hyperplasia in the middle ear epithelium are the hallmarks of otitis media, especially in otitis media with effusion
It is the histopathologic basis for mucin or mucin-like glycoprotein production in the middle ear cavity, which contributes to the accumulation of middle ear fluid and compromises middle ear function
Summary
Goblet cells are mucus secretory cells that are scattered among the columnar cells near the Eustachian tube orifice in the middle ear epithelium. Their main function is to secrete mucins, forming the mucus layer, which surrounds the cilia and builds up the mucociliary transportation clearance system on the middle ear epithelial surface. The role of Notch signalling in proliferation and differentiation in airway epithelial cells has been actively studied[11]. We report that goblet cell metaplasia is linked to the suppression of the Notch signal pathway in mouse otitis media. The aim of this study is to find out ways to restrain mucous cells metaplasia, and to provide theoretical basis for the prevention and treatment of otitis media
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